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Metabolite Alterations in the Left Dorsolateral Prefrontal Cortex and Its Association With Cognitive Assessments in Amyotrophic Lateral Sclerosis: A Longitudinal Magnetic Resonance Spectroscopy Study Publisher Pubmed



Ghaderi S1, 2 ; Fatehi F2, 3 ; Kalra S4, 5 ; Okhovat AA2 ; Nafissi S2 ; Mohammadi S2 ; Batouli SAH1
Authors
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Authors Affiliations
  1. 1. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Neuromuscular Research Center, Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Neurology Department, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
  4. 4. Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada
  5. 5. Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada

Source: Brain Research Bulletin Published:2024


Abstract

Objective: To characterize the longitudinal metabolite profile of the left dorsolateral prefrontal cortex (DLPFC) in amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS) and to examine its correlation with cognitive assessments. Methods: Thirteen patients at baseline and ten at follow-up, along with 14 age-, sex-, and handedness-matched healthy controls (HCs), were recruited. Three Tesla with a 64-channel coil, Point-RESolved Spectroscopy (PRESS) sequence (TR=1500 ms and TE=140 ms) was used. Metabolites in the left DLPFC were quantified using LCModel. Cognitive performance and functional impairment were assessed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) and Revised ALS Functional Rating Scale (ALSFRS-R), respectively. Group comparisons were adjusted for multiple comparisons (p < 0.05, Bonferroni correction). The links between the brain metabolites and cognitive function were investigated using relevant correlation tests (Pearson's or Spearman's). Results: Our analysis revealed a significant difference in the choline-to-creatine ratio (tCho/tCr) among the three groups. Baseline ALS patients showed a higher tCho/tCr ratio than HCs (p = 0.033, Bonferroni-corrected). Interestingly, the total N-acetyl aspartate (tNAA)/tCr ratio, a marker of neuronal health, was strongly positively correlated with visuospatial cognitive scores at baseline and follow-up. Furthermore, at follow-up, tNAA/tCr was positively correlated with the total scores and specific sub-scores on the ECAS, encompassing both ALS-specific and non-specific cognitive domains. At follow-up, positive correlations emerged between tNAA/tCr and the total language and executive function scores. Conclusions: Metabolite alterations and correlations with cognition were observed in the left DLPFC of ALS patients, supporting extra-motor involvement and its association with cognitive decline. © 2024 The Authors
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